HBP1 - Der Repressor HMG-Box-Transkriptions-Faktor-1 in der Hämatopoese und bei akuter myeloischer Leukämie

Proliferation, survival and differentiation of hematopoietic cells are regulated by different transcription factors. Any aberrant signalling in the process of hematopoiesis can cause leukemic transformation. In this project we tested the hypothesis that the transcription factor HBP1 (HMG-Box containing protein 1) plays an important role in the regulation of hematopoiesis, as there is evidence indicating that HBP1 is involved in the pathogenesis of acute myeloid leukaemia. By flow cytometry, human bone marrow cells from healthy donors were sorted into HSCs (hematopoietic stem cells), CMPs (common myeloid progenitors) and GMPs (granulocyte megakaryocyte progenitors). These cell types represent progressing stages in the process of myeloid differentiation. In these populations we investigated HBP1 mRNA expression by quantitative PCR. Secondly, we screened blasts of acute myeloid leukemia (AML) for their HBP1 expression. Additionally, studies in leukemic cell lines were conducted (knock-down of HBP1, cell cycle analysis) to gain information about the functional role of HBP1 in malignant hematopoiesis. In summary, we showed that HBP1 is highly expresses in hematopoieitic stem cells and that HBP1-expression decreases during the maturation of hematopoietic cells. Out data indicate that HBP1 is important for stem cell functioning in normal hematopoiesis and myeloid differentiation.